Know Cancer

forgot password

A Phase I Study of Hepatic Arterial Infusion of Escalating Dose Melphalan With Venous Filtration for Metastatic Unresectable Cancers of the Liver

Phase 1
14 Years
Not Enrolling
Liver Cancer, Metastatic Cancer

Thank you

Trial Information

A Phase I Study of Hepatic Arterial Infusion of Escalating Dose Melphalan With Venous Filtration for Metastatic Unresectable Cancers of the Liver


- Determine the dose-limiting toxicity and maximum tolerated dose of hepatic arterial
infusion with melphalan in patients with unresectable liver cancer.

- Determine the regional and systemic toxic effects of this drug in these patients.

- Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients undergo percutaneous hepatic arterial infusion, using a double balloon catheter in
the inferior vena cava to isolate circulation to the liver, with melphalan over 30 minutes
on day 1. Treatment may be repeated when all toxic effects are grade 2 or less. Patients
undergo staging at 4 weeks after completion of the second treatment. Patients may receive 2
additional treatments.

Cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 12 additional
patients are treated with melphalan at the recommended dose.

Patients are followed every 3 months for 2 years and then every 4 months for 1 year.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Inclusion Criteria


- Histologically or cytologically confirmed unresectable cancer of the parenchyma of
the liver

- Liver metastases allowed

- Limited unresectable extrahepatic disease (including but not limited to the
following) is allowed provided the life-threatening component of progressive disease
is in liver:

- Up to 4 pulmonary nodules each less than 1 cm in diameter

- Retroperitoneal lymph nodes less than 3 cm in diameter

- Fewer than 10 skin or subcutaneous metastases less than 1 cm in diameter

- Asymptomatic bone metastases that have been or can be palliated with

- Solitary metastasis to any site that can be resected

- Prior therapy with intrahepatic perfusion with or without hepatic arterial infusion
with floxuridine is allowed provided patient had a radiographic partial response of
3-months duration



- 14 and over

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified


- Platelet count greater than 100,000/mm^3

- Absolute neutrophil count at least 1,300/mm^3

- Hematocrit greater than 27%


- Bilirubin no greater than 2.0 mg/dL

- PT within 2 seconds of upper limit of normal

- No biopsy-proven cirrhosis with evidence of portal hypertension by history,
endoscopy, or radiologic study


- Creatinine no greater than 1.5 mg/dL OR

- Creatinine clearance greater than 60 mL/min


- No prior congestive heart failure with LVEF less than 40%


- No chronic obstructive pulmonary disease

- No other chronic pulmonary disease

- FEV_1 at least 30% of predicted

- DLCO at least 40% of predicted


- Weight greater than 35 kg

- HIV negative

- No active infections

- No severe allergic reaction to iodine contrast not controlled by antihistamines or

- No known prior hypersensitivity reaction to melphalan

- Not pregnant or nursing

- Negative pregnancy test


Biologic therapy:

- At least 1 month since prior biologic therapy for the malignancy and recovered


- See Disease Characteristics

- At least 1 month since prior chemotherapy for the malignancy and recovered

Endocrine therapy:

- Not specified


- See Disease Characteristics

- At least 1 month since prior radiotherapy for the malignancy and recovered


- Not specified


- No concurrent chronic anticoagulants

- No concurrent immunosuppressive drugs

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

H. Richard Alexander, MD, FACS

Investigator Role:

Study Chair

Investigator Affiliation:

NCI - Surgery Branch


United States: Federal Government

Study ID:




Start Date:

July 2001

Completion Date:

Related Keywords:

  • Liver Cancer
  • Metastatic Cancer
  • localized unresectable adult primary liver cancer
  • advanced adult primary liver cancer
  • recurrent adult primary liver cancer
  • liver metastases
  • Liver Neoplasms
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary



Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support Bethesda, Maryland  20892-1182